GALACTIC-HF: Omecamtiv mecarbil effective in patients with severe HF
In a post hoc analysis of the GALACTIC-HF trial, omecamtiv mecarbil reduced the primary endpoint of time to first HF event or CV death among patients with severe HF.
The initial findings of the global double-blind, placebo-controlled phase 3 randomized GALACTIC-HF trial were previously reported by Healio.
For the present analysis published in JAMA Cardiology, G. Michael Felker, MD, MHS, FHFSA, professor of medicine and vice chief for clinical research of Duke Cardiology and director of cardiovascular research at the Duke Clinical Research Institute, and colleagues sought to determine the safety and effectiveness of omecamtiv mecarbil (Cytokinetics) in patients with vs. without severe HF. They defined severe HF as the presence of NYHA symptom class III to IV, left ventricular ejection fraction of 30% or less and hospitalization for HF within the previous 6 months.
Time to first HF event or CV death served as the primary outcome, with time to CV death and safety and tolerability serving as secondary endpoints.
The analysis included 2,258 patients (mean age, 65 years; 79% men) who met the specified criteria for severe HF from 8,232 patients enrolled in GALACTIC-HF. Among these patients, 1,106 were randomly assigned to omecamtiv mecarbil and 1,152 to placebo.
Interaction by severity
Results revealed that omecamtiv mecarbil significantly reduced the primary endpoint in patients with severe HF (HR = 0.8; 95% CI, 0.71-0.9), but had no significant impact in patients without severe HF (HR = 0.99; 95% CI, 0.91-1.08; P = .005 for interaction). Reductions in CV death were also observed for patients with severe HF (HR = 0.88; 95% CI, 0.75-1.03) compared with those without severe HF (HR = 1.1; 95% CI, 0.97-1.25; P = .03 for interaction).
“Omecamtiv mecarbil therapy was well tolerated in patients with severe HF,” the researchers wrote, “with no significant changes in blood pressure, kidney function or potassium level compared with placebo. ... These data support both the efficacy and tolerability of omecamtiv mecarbil in a patient population that may be difficult to treat effectively with other HF drugs.”
‘Actionable clinical dilemma’
In an accompanying editorial, Clyde W. Yancy, MD, MSc, MACC, FAHA, MACP, FHFSA, vice dean for diversity and inclusion, chief of cardiology, Magerstadt Professor and professor of medicine and medical social sciences at Northwestern University Feinberg School of Medicine and past president of the American Heart Association, and colleagues wrote that this analysis provides an important statement about the potential benefits and risks related to omecamtiv mecarbil therapy. But more importantly, they wrote, it also provides a clinically evident demarcation of a potentially new HF stage, “specifically patients with [HF with reduced ejection fraction] who are receiving effective guideline-directed medical therapy (ie, patients with stage C HF) but have progressive or severe symptoms that do not yet reach the threshold for advanced therapies (ie, stage D HF). This demarcation is not a quirk of recruitment within a large clinical trial but a true, common and actionable clinical dilemma.”
Yancy, who is also deputy editor of JAMA Cardiology, and colleagues noted that despite the limitations of being conducted post hoc, this analysis “offers direction that may guide the use of a new therapy, identify an important and expanding patient population with severe HF, and offer the potential for salutary clinical benefits.”